Long range order and molecular organization in normal and virus-transformed cell membranes will be investigated and compared by studying both the transverse and the lateral distribution of selected components. A number of simple membrane systems and tissue culture cell membranes will be probed using a combination of electron microscopic and biochemical techniques. A novel combination of autoradiography and freeze-etching will be developed and used to measure membrane asymmetry and in-plane heterogeneity. Bulk freeze-fracture methods will be perfected and applied to provide an entirely new measure of the relative concentration of specific lipids or proteins in either the inside or outside half of a membrane. Freeze-fracture and freeze-etching techniques together with immunochemical labelling methods will be used to study the distribution of membrane surface components and to relate the mobility of protein and glycoprotein at membrane surfaces to the mobility of underlying structures in the lipid bilayer. Cells or their isolated membranes will be subjected to a variety of environments, hydrolytic chemicals and other manipulations to identify the factors responsible for controlling membrane mobility or maintaining patterns of asymmetry or in-plane distribution of components during normal and malignant growth. BIBLIOGRAPHIC REFERENCES: Branton, D. et al. Freeze-etching nomenclature. Science 190:54-56 (1975).